The novel capsid-binding antiviral pleconaril inhibits in vitro replication of most rhinoviruses and enteroviruses. Oral pleconaril treatment was studied in 2 parallel randomized, double-blind, placebo-controlled trials. Among 1363 picornavirus-infected participants (65%) in the studies combined, the median time to alleviation of illness was 1 day shorter for pleconaril recipients than for placebo recipients ( ). Cold symptom P ! .001 scores and frequency of picornavirus cultured from nasal mucus specimens were lower among pleconaril recipients by day 2 of treatment. No treatment effects were seen in those without picornavirus infection. Pleconaril was associated with a higher incidence of nausea (6% vs. 4%) and diarrhea (9% vs. 7%) and with small increases in mean serum cholesterol levels and platelet counts, compared with baseline measurements. A subsequent 6-week prophylaxis study found that pleconaril induces cytochrome P-450 3A enzymes, which metabolize a variety of drugs, including ethinyl estradiol. Early pleconaril treatment was well tolerated and significantly reduced the duration and severity of colds due to picornaviruses in adults.The majority of common colds are due to picornaviruses, principally rhinoviruses (1100 serotypes) and, less often, enteroviruses (у67 serotypes), which to-

No abstract

We evaluated the efficacy and tolerability of oral pleconaril, an anti-picornavirus agent, in treating acute viral respiratory illness (VRI) in two double-blind, placebo-controlled trials. Otherwise healthy subjects, 14 years of age or older, who presented within 36 h of VRI symptom onset, were randomized to pleconaril 400 mg or matching placebo in liquid (first trial) or tablet (second trial) formulations twice-daily (first trial only) or three-times daily for 7 days. The infected subjects from the corresponding active and placebo groups (three-times daily dosing regimens) were combined for analysis. Among the subset of subjects with proven picornaviral infection in both studies (42% of total enrolled), pleconaril 400 mg three-times daily ( n=323) reduced the time to alleviation of illness (no rhinorrhoea and other symptoms mild or absent for ≥48 h) compared with placebo ( n=264) (median: 10.0 days for placebo and 8.5 days for pleconaril; P=0.029). In addition, pleconaril reduced the time to a ≥50% reduction from baseline in total symptom severity score (median: 4.5 days for placebo and 3.5 days for pleconaril; P=0.038). Significant reductions in the number of tissues used for nose-blowing (20% reduction) and in nights of disturbed sleep (16% reduction) were also observed. Pleconaril was generally well tolerated; the liquid formulation caused gastrointestinal disturbance in all groups (diarrhoea 10–14%, nausea 5–9%, abdominal discomfort 6–8%), and tablets were associated with a greater incidence of nausea (3% for placebo versus 7% for pleconaril, P=0.003). Pleconaril 400 mg administered three-times daily reduced the duration and severity of picornaviral VRI in adolescents and adults.